Breast cancer is a malignant tumor originating from breast tissue, most commonly from the epithelium lining milk ducts or the lobules that supply the ducts with milk. Breast cancer is reported to occur at a higher rate in women of advanced countries than do other cancers.
Various etiologic factors for breast cancer are now being mentioned, including female hormones, cancer history, family history, lack of having borne a child, dietary habit, etc., without no clear relationship with these has been proven thus far.
In South Korea, breast cancer ranks second after stomach cancer in frequency and fifth after breast cancer, liver cancer, uterine cancer and lung cancer in mortality for women. Breast cancer cases of women in South Korea have rapidly increased every year as have those of Western countries. Recently, breast cancer cases in South Korea are reported to have rapidly increased. A survey report of the Statistics Korea has it that breast cancer cases exceeded uterine cervical cancer cases in 1998 and accounted for 16.1% of women's cancer cases in 2001, ranking first before stomach cancer. In addition, the incident rate of breast cancer was 11.1% between 2001 and 2002, which was greater than that of other cancers. Now, the high incident rate of breast cancer is thought to be associated with various factors. Among them are a low birthrate, breastfeeding for a short period of time, early menarche, late menopause, the westernization of dietary habits, and the pollution of living environment. Further, glandular tissue of women who had been stimulated by female hormones at rapidly increased frequency at the time of their physiologically active change was increased in sensitivity and these individuals may be confronted with a greater likelihood of being struck by breast cancer.
The incidence of breast cancer and the mortality from breast cancer in Korea are expected to increase for a significant period of time in the future in consideration of the trend of because of the westernization of living. As they grow, breast cancer cells, like other cancer cells, generally infiltrate adjacent tissues or metastasize into the lymph nodes. In most breast cancer cases, the patients did not have many detectable symptoms or they did not examine their breasts by themselves. Therefore, it is very important to effectively diagnose early breast cancer to reduce mortality from breast cancer.
To decrease the mortality from breast cancer, early diagnosis is the most important thing. It is also important to do an adjuvant therapy that is suitable in light of the prognosis after the primary initial treatment. For the diagnosis of breast cancer, various methods are used in combination. So far, breast self-examination has accounted for 70% of breast cancer cases. However, it is impossible to discriminate malignant breast tumors from benign tumors by giving breast self-examination. A number of breast cancer screening tests have been employed including X-ray mammography, ultrasound, fine-needle aspiration cytology, and magnetic resonance imaging. Eventually, biopsy is employed to diagnose breast cancer. Mammographic screening for breast cancer uses X-rays to examine the breast. Mammography is effective at determining whether breast tumors are benign or malignant and can detect hidden tumors. This method is one of the most effective techniques by which early breast cancer can be diagnosed before the detection of a lump by breast self-examination. However, mammography is disadvantageous in that diagnostic accuracy is lowered for a breast in which the mammary gland is highly developed or which is a small and dense breast with highly fibrous tissue, like the breasts of young women. In addition, there is a dispute waging about that more frequent mammograms run the risk of significantly increasing breast cancer because of the radiation. As an alternative to mammography, ultrasonography is employed. Ultrasonography can effectively discriminate cystis from lumps, but is ineffective in telling malignant tumors from benign tumors. Ultrasonography can effectively discriminate cystis from lumps, but is ineffective in telling malignant tumors (cancer) from benign tumors (non-cancer). In practical clinics, the finding of abnormalities requires the use of fine-needle aspiration and magnetic resonance imaging for more accurate diagnosis. Even these methods, however, cannot guarantee that malignant tumors (cancer) can be distinguished from benign tumors (non-cancer) although they can reveal morphological differences between normal and abnormal tissues. Ultimately, a biopsy is employed to diagnose breast cancer decisively.
To supplement such breast screening methods, attempts have been made to use blood tumor marker levels to diagnose breast cancer. Although studied for their values as diagnosis or prognosis factors, the application of conventional tumor markers is accompanied by limitations, and there are no officially recommended breast cancer markers.
Thioredoxin (Trx) was discovered as a coenzyme that donates a hydrogen ion to ribonucleotide reductase, an enzyme essential for DNA synthesis in Escherichia coli. Characterized by the active site -Cys-Gly-Pro-Cys- (SEQ ID NO: 5) in which the two vicinal cysteine residues interchangeably exist between the oxidized form of a disulfide bond (S—S) and the reduced form of a dithiol (—SH—SH), Trx functions as an intracellular oxidoreduction controller. Thioredoxin (Trx) is a 12 kDa oxidoreductase thatis kept in the reduced state by thioredoxin reductase in a NADPH-dependent reaction. There are two kinds of mammal thioredoxins: thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2). Thioredoxins act as electron donors to peroxidases so that, for example, toxic hydrogen peroxide can be eliminated. Also, thioredoxins provide electrons for ribonucleotide reductase. Thioredoxins plays a role in binding transcription elements to DNA in bacteria while they have an influence on the activity of NF-kB (nuclear transcription factor kB) in eukaryotes. Therefore, thioredoxins are associated with cell death and tumor cells, and play an important role in regulating the growth of tumor cells. Serving as a general disulfide oxidoreductase, thioredoxin facilitates the reduction of other proteins by a redox mechanism based on reversible reduction of a disulfide to two cysteine thiol groups, thereby recovering the normal function of the proteins. In mammalian cells, thioredoxin 1 and 2 are also involved in the regulation of nitric oxide levels and thus in cell death. Therefore, the enzymes are potentially important in conjunction with the onset of many diseases including inflammatory diseases, heart failure, cancer, etc. Immunohistochemical analysis with anti-thioredoxin antibodies revealed the expression of thioredoxins in cancer cells in various tissues such as the liver, colon, pancreas, and the uterine cervix, indicating the implication of thioredoxins in oncogenesis.
There has been a need for a diagnostic marker and a method for breast cancer that allows the accurate diagnosis of early breast cancer and allows the prognosis of breast cancer to be made. Almost few studies have been done on the use of thioredoxin 1 as a diagnostic marker for breast cancer.